Transient upregulation of TASK-1 expression in the hypoglossal nucleus during chronic intermittent hypoxia is reduced by serotonin 2A receptor antagonist.

Abstract

Hypoglossal motoneurons innervate genioglossus muscle, the contraction of which is critical in the maintenance of upper airway patency in patients with obstructive sleep apnea. As a potassium channel distributed in hypoglossal motoneurons, TWIK-related acid-sensitive K+ channel-1 (TASK-1) could be inhibited by 5-HT. This study aimed to investigate if TASK-1 expression in hypoglossal nucleus could be influenced by chronic intermittent hypoxia (CIH) and 5-HT2A receptors antagonist. Two hundred twenty-eight rats were exposed to CIH or normoxia (NO) in the presence and absence of 5-HT 2A receptor antagonist (MDL-100907) microinjected into the hypoglossal nucleus. The expression of 5-HT and TASK-1 in the hypoglossal nucleus were detected by immunohistochemistry and reverse transcription quantitative polymerase chain reaction on the 1st, 3rd, 7th, 14th and 21st day of CIH exposure. The mean optical density (MOD) of 5-HT in the XII nucleus was significantly increased in the CIH and CIH + MDL group than the NO group on the 7th and 21st day ( p < 0.05). Compared with the NO group, the MOD and gene expression of TASK-1 in the CIH group was significantly increased on the 7th and 14th day ( p < 0.05), then normalized on the 21st day. The TASK-1 expression in the CIH + MDL group was significantly lower than the CIH + PBS and CIH group on the 7th and 14th day ( p < 0.05). The CIH-induced transiently upregulation of the TASK-1 expression in the hypoglossal nucleus could be reversed by 5-HT 2A receptor antagonist, indicating that the modulation of the TASK-1 expression in response to CIH involves 5-HT and 5-HT 2A receptors, and this CIH effect might be 5-HT 2A receptor-dependent.